Evidence map›Paper›PMID 37200809›Full record

ArticleACS pharmacology & translational science2023

Discovery of 5'-Substituted 5-Fluoro-2'-deoxyuridine Monophosphate Analogs: A Novel Class of Thymidylate Synthase Inhibitors.

Madhuri Dasari, Stephen C Pelly, Jiafeng Geng, Hannah B Gold, Nicole Pribut, Savita K Sharma, Michael P D'Erasmo, Perry W Bartsch, Carrie Sun, Kiran Toti and 6 more

Open access · hybridAbstract read
In one paragraph

Article in ACS pharmacology & translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. The Red AlgaCurrent issues in molecular biology · 2026
    Article
  2. Review
  3. Article
  4. International journal of molecular sciences · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Madhuri DasariDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.
Stephen C PellyDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.ORCID https://orcid.org/0000-0001-5930-4939
Jiafeng GengDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.ORCID https://orcid.org/0000-0001-9488-0974
Hannah B GoldDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.
Nicole PributDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.ORCID https://orcid.org/0000-0003-0439-9162
Savita K SharmaDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.
Michael P D'ErasmoDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.
Perry W BartschDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.
Carrie SunDepartment of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Kiran TotiDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.ORCID https://orcid.org/0000-0002-4528-4858
Rebecca S ArnoldDepartment of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
John A PetrosDepartment of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Lingjie XuJunrui Biotechnology, Hangzhou, Zhejiang 310000, China.
Yi JiangJunrui Biotechnology, Hangzhou, Zhejiang 310000, China.
Eric J MillerWinship Cancer Institute, Emory University, Atlanta, Georgia 30322, United States.ORCID https://orcid.org/0000-0003-3659-0105
Dennis C LiottaDepartment of Chemistry, Emory University College of Arts and Sciences, Atlanta, Georgia 30322, United States.ORCID https://orcid.org/0000-0002-7736-7113
Florida State University · USEmory University · US

Funding

Medical Scientist Training ProgramT32GM142617 · NIGMS · EMORY UNIVERSITY · PI Jason Yustein · 2022 to 2026
$7.0M
NIGMS NIH HHS T32 GM142617
6 · The paper itself

Abstract

5-Fluorouracil and 5-fluorouracil-based prodrugs have been used clinically for decades to treat cancer. Their anticancer effects are most prominently ascribed to inhibition of thymidylate synthase (TS) by metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). However, 5-fluorouracil and FdUMP are subject to numerous unfavorable metabolic events that can drive undesired systemic toxicity. Our previous research on antiviral nucleotides suggested that substitution at the nucleoside 5'-carbon imposes conformational restrictions on the corresponding nucleoside monophosphates, rendering them poor substrates for productive intracellular conversion to viral polymerase-inhibiting triphosphate metabolites. Accordingly, we hypothesized that 5'-substituted analogs of FdUMP, which is uniquely active at the monophosphate stage, would inhibit TS while preventing undesirable metabolism. Free energy perturbation-derived relative binding energy calculations suggested that 5'(

Identifiers

PMID37200809
PMCPMC10186355
OpenAlexW4321606344

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.